2-C-Methyl-D-erythritol 4-phosphate cytidylyltransferase is an essential enzyme in the mevalonate-independent pathway of isoprenoid biosynthesis. The structure of a tetragonal crystal form has been solved by molecular replacement and refined to 2.4 A resolution. Structure and sequence comparisons suggest that the enzyme is a suitable target for a structure-based approach to the development of novel broad-spectrum antibiotics. However, the absence of ligands in the enzyme active site together with the moderate resolution of the structure indicates that this tetragonal crystal form is inferior to that of a previously reported highly ordered monoclinic form [Richard et al. (2001), Nature Struct. Biol. 8, 641-647].